PROJECT SUMMARY/ABSTRACT The Crump Institute for Molecular Imaging at UCLA has a long and successful track record in the development of molecular imaging technologies. These innovations have led to the creation of the Crump Preclinical Imaging Technology Center, a campus-wide shared resource facility for in vivo imaging technologies and services. This site is supported by a diverse faculty with considerable expertise in imaging physics, biomarker development and preclinical imaging, as evidenced by the extensive publication record employing our imaging technologies. This proposal requests funds to acquire the Sofie GNEXT integrated PET/CT system, a new state-of-the-art small animal imaging system with integrated positron emission tomography (PET) and computed tomography (CT) capabilities. This multi-modality system includes the highest resolution and sensitivity PET system commercially available and a high resolution CT designed for routine animal imaging with low radiation dose exposure. These improvements enable the UCLA research community to study diseases in small animals at early, more clinically relevant stages, heterogeneity of tissues and malignancies, and subcortical structures of the rodent brain. It will offer 8 times higher dynamic range, 10 times larger field of view, and 3.5-folder higher volumetric resolution than currently available on our G8 PET/CT. These are all applicable to our Major and Minor User projects discussed in the proposal. Furthermore, our investigators will be able to access a larger panel of PET tracers and study novel biomarkers in vivo at earlier stages, both of which are otherwise restricted by limitations in radiochemistry such as low yields and/or low specific activities. The large 12-cm diameter field of view of both PET and CT enables imaging of large rats and up to four mice, which improves throughput and experimental statistics. Our G8 PET/CT is designed only for mouse-sized whole body imaging and does not offer high-resolution CT capabilities. The GNEXT system will replace older and unsupported stand-alone PET and CT systems that have seen increasing downtime in recent years and are no longer considered state-of-the-art. Basic operating costs and staff salaries are supported through sales- and-service recharges and grants from the Jonsson Comprehensive Cancer Center and the NanoSystems Biology Cancer Center. Institutional support is provided to offset any difference in cost of GNEXT after applicable taxes. Our Advisory Committee, the Resource Allocation Committee, meets on a weekly basis and will continue to do so to resolve scheduling conflicts and disputes should they arise. Our shared resource facility has extensive experience in preclinical PET/CT imaging and our director and full-time staff will continue to provide user trainings through regular workshops and didactic graduate courses in the Department of Molecular and Medical Pharmacology. Our broad expertise in PET and CT imaging technologies and access to on-site, routine (daily) PET tracer productions ensures the extensive and effective use of the GNEXT PET/CT and continued access to state-of-the-art imaging for the UCLA research community.